1. Field of the Invention
The present invention relates generally to a method of producing composite particles, and specifically to a method of producing composite particles comprising a polymer and a biologically active material via supercritical fluid processing.
2. Description of Related Art
Conventional methods of preparing composite or single material polymer particles include spray drying, and jet milling. Further, particles have been produced from emulsions using techniques such as emulsion polymerization, emulsion evaporation, and solvent extraction of emulsions. Typical spray drying techniques involve evaporation of a solvent containing the polymer using hot air. The high temperatures employed for such processing can sometimes degrade thermally labile drugs and polymers. Furthermore, the particles obtained by spray drying typically have a broad size distribution, usually in the micron range.
Jet milling is a technique used to produce small particles, however, such particles tend to have undesirably broad size distributions. Only a small fraction of the particles produced using jet milling have a size that is in a desired nanometer range. Additionally, the shearing energy required for jet milling can degrade some biologically active materials and polymers.
As noted above, conventional techniques are available that produce particles from emulsions. The conventional production methods include emulsion polymerization, emulsion evaporation, emulsion extraction, and vacuum distillation of emulsions. With reference to emulsion polymerization, small particles are prepared from free-radical polymerizable monomers by using a polymerization process in the presence of water. Emulsion polymerization has an unfortunate side effect that undesirable materials, such as residual monomers, oligomers and initiators, remain in the suspension.
The emulsion evaporation process can produce a nanoparticle suspension, but the process has several drawbacks. One of the drawbacks is that the process proceeds at an undesirably slow rate—exceeding 4 hours in some instances. In the emulsion extraction process, organic solvents are used that have raised concerns about possible environmental and health affects arising from residual solvent in the particles produced.
Solvent or emulsion extraction of water-in-oil-in-water (W/O/W) emulsions has been used to obtain small particles. Unfortunately, the emulsion extraction process requires large amounts of solvent for extraction, which leads to large waste streams, increased cost and residual solvent toxicity. Similarly, dilution by water of oil-in-water (O/W) emulsions prepared using partially water soluble organic solvents can obtain small particles. But, this method can result in low polymer concentrations in the final dispersion and uses undesirably large quantities of water.
Vacuum distillation has produced particles from emulsions, but the associated high operating cost makes this process economically undesirable. In addition, the processing times required for achieving a low residual solvent content in particles produced by this method is lengthy.
In view of the limitations of prior art processing methods, it would be desirable to produce particles using a technique that can result in particles having a decreased particle size in a narrow size distribution range, a reduced processing time and a reduced cost, and that does not damage or degrade the components. It would be further desirable to produce particles without using undesirably large amounts of solvent.